rs4732516

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001395413.1(POR):c.1058-13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 1,611,828 control chromosomes in the GnomAD database, including 710,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 57007 hom., cov: 33)

Exomes 𝑓: 0.94 ( 653371 hom. )

Consequence

POR
NM_001395413.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.76

Publications

15 publications found

Variant links:

Genes affected

POR (HGNC:9208): (cytochrome p450 oxidoreductase) This gene encodes an endoplasmic reticulum membrane oxidoreductase that is essential for multiple metabolic processes, including reactions catalyzed by cytochrome P450 proteins for metabolism of steroid hormones, drugs and xenobiotics. The encoded protein has a flavin adenine dinucleotide (FAD)-binding domain and a flavodoxin-like domain which bind two cofactors, FAD and FMN, that allow it to donate electrons directly from NADPH to all microsomal P450 enzymes. Mutations in this gene cause a complex set of disorders, including apparent combined P450C17 and P450C21 deficiency, amenorrhea and disordered steroidogenesis, congenital adrenal hyperplasia and Antley-Bixler syndrome, that resemble those caused by defects in steroid metabolizing enzymes such as aromatase, 21-hydroxylase, and 17 alpha-hydroxylase. [provided by RefSeq, Aug 2020]

POR Gene-Disease associations (from GenCC):

Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Antley-Bixler syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

POR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 7-75984764-C-G is Benign according to our data. Variant chr7-75984764-C-G is described in ClinVar as Benign. ClinVar VariationId is 138789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395413.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POR	NM_001395413.1	MANE Select	c.1058-13C>G	intron	N/A	NP_001382342.1	P16435
POR	NM_001382655.3		c.1112-13C>G	intron	N/A	NP_001369584.2
POR	NM_001367562.3		c.1058-13C>G	intron	N/A	NP_001354491.2	P16435

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POR	ENST00000461988.6	TSL:1 MANE Select	c.1058-13C>G	intron	N/A	ENSP00000419970.2	P16435
POR	ENST00000447222.5	TSL:5	c.1217-13C>G	intron	N/A	ENSP00000393527.1	H0Y4R2
POR	ENST00000910548.1		c.1058-13C>G	intron	N/A	ENSP00000580607.1

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129552

AN:

152008

Hom.:

56976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.923

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.973

Gnomad EAS

AF:

0.855

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.978

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.878

GnomAD2 exomes

AF:

0.911

AC:

225464

AN:

247390

AF XY:

0.921

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.840

Gnomad ASJ exome

AF:

0.975

Gnomad EAS exome

AF:

0.853

Gnomad FIN exome

AF:

0.977

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.933

GnomAD4 exome

AF:

0.944

AC:

1377896

AN:

1459702

Hom.:

653371

Cov.:

AF XY:

0.945

AC XY:

686189

AN XY:

726174

show subpopulations

African (AFR)

AF:

0.596

AC:

19907

AN:

33428

American (AMR)

AF:

0.848

AC:

37916

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.974

AC:

25450

AN:

26116

East Asian (EAS)

AF:

0.862

AC:

34210

AN:

39692

South Asian (SAS)

AF:

0.920

AC:

79319

AN:

86244

European-Finnish (FIN)

AF:

0.975

AC:

50794

AN:

52090

Middle Eastern (MID)

AF:

0.943

AC:

5432

AN:

5762

European-Non Finnish (NFE)

AF:

0.962

AC:

1069111

AN:

1111356

Other (OTH)

AF:

0.924

AC:

55757

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

3614

7228

10842

14456

18070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21564

43128

64692

86256

107820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.852

AC:

129635

AN:

152126

Hom.:

57007

Cov.:

AF XY:

0.854

AC XY:

63476

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.610

AC:

25284

AN:

41458

American (AMR)

AF:

0.871

AC:

13320

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

3377

AN:

3472

East Asian (EAS)

AF:

0.855

AC:

4387

AN:

5128

South Asian (SAS)

AF:

0.919

AC:

4442

AN:

4832

European-Finnish (FIN)

AF:

0.978

AC:

10393

AN:

10624

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.963

AC:

65463

AN:

67998

Other (OTH)

AF:

0.878

AC:

1853

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.916

Hom.:

11938

Bravo

AF:

0.832

Asia WGS

AF:

0.859

AC:

2988

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency (2)

ADRENAL HYPERPLASIA, CONGENITAL, DUE TO 21-HYDROXYLASE DEFICIENCY (1)

Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.22

(source)

DANN

Benign

0.38

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over